Mouse cells transformed in vitro with SV40 virus are in general rapidly rejected in vivo. Evidence from other laboratories suggests that rejection is mediated by a T lymphocyte response to the SV40-specific transplantation antigen. We and others find both T cytotoxic cells (CTL) and delayed hypersensitivity (DTH) responses to SV40 cells, but the relative role of these mechanisms in tumor rejection is unknown. We have recently isolated variants of an SV40-transformed C3H cell line that differ in their susceptibility to lysis in vitro with syngeneic anti-SV40 CTL or LPS-activated macrophages. The lines also differ in their ability to produce tumors in vivo. These lines present a unique opportunity to investigate the cellular mechanisms involved in refjection of SV40 tumors. Based on these studies the working hypothesis is proposed that while either CTL or DTH mechanism can produce secondary rejection of SV40 tumors in SV40-immune mice, both mechanisms acting in concert are necessary for primary rejection of tumors in non-immune recipients. To test this hypothesis cloned SV40 lines of differing immunosensitivities, as determined by in vitro assay, will be tested for growth in naive and immune recipients. These experiments will employ strains of mice previously found to be CTL responders or non-responders to SV40. We will develop assays of the DTH and Lytl+ in vitro proliferation response to SV40 to determine whether we can detect H-2 region control of this response as well. Information gained from these studies willbe used in the design of adoptive transfer experiments to test directly the roles of CTL and DTH responses to immune elimination of SV40 tumors. The overall goal of these studies is to begin to dissect tumor-eliminating T cell responses in vivo to a single tumor-associated antigen (SV40 T antigen) as a function of the genetically determined ability to respond to that antigen.